Electrical therapy applied to the brain with increased efficacy and/or decreased undesirable side effects, and associated systems and methods

ABSTRACT

Electrical therapy applied to the brain with increased efficacy and/or decreased undesirable side effects, and associated systems and methods, are disclosed. A representative method includes applying a therapy signal to a patient, via at least one electrode at a subdural or epidural location at the patient&#39;s brain, to provide effective therapy that reduces or eliminates the effects of a patient disorder. The therapy signal does not induce any non-therapeutic side effects, and has a frequency in a frequency range of from 1.2 kHz to 500 kHz, an amplitude in an amplitude range from 0.1 to 20 mA, and a pulse width in a pulse width range from 1 microsecond to 400 microseconds.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application in continuation of U.S. patent application Ser.No. 16/127,098, file Sep. 10, 2018, which claims priority to U.S.Provisional Application 62/556,183, filed on Sep. 8, 2017, and U.S.Provisional Application 62/643,128, filed on Mar. 14, 2018, both ofwhich are incorporated herein by reference.

TECHNICAL FIELD

The present disclosure is directed generally to electrical therapyapplied to the brain with increased efficacy and/or decreasedundesirable side effects, and associated systems and methods.

BACKGROUND

Deep brain stimulation (DBS) and cortical stimulation have been used foryears to treat a variety of patient indications. In a typical DBSprocedure, an electrical probe is inserted into the patient's brain andactivated at a frequency generally under 1,200 Hz, and more typically atabout 130 Hz. This relatively low frequency can synchronize neuralfirings in the brain and can reduce some of the effects of the patient'smotor dysfunctions. For example, patients suffering from tremors canexperience reduced symptoms as a result of the electrical stimulation.However, the stimulation can produce undesired side effects. Sucheffects can include unwanted sensory effects (e.g., paresthesia),unwanted motor effects (e.g., an inability to initiate movement,uncontrolled movement), disturbed speech, and/or unwanted cognitiveeffects (e.g., an inability to focus one's thoughts). Accordingly, thereremains a need for improved therapies for motor dysfunctions and otherneurological conditions and/or patient indications.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a partially schematic, partially cut-away illustration of apatient's head, illustrating a representative system configured inaccordance with some embodiments of the present technology.

FIG. 2 is a partially schematic, cross-sectional illustration of apatient's brain, illustrating cortical implantation techniques, inaccordance with some embodiments of the present technology.

FIG. 3 is a flow diagram illustrating a representative process inaccordance with some embodiments of the present technology.

FIGS. 4A-4B illustrate a deep brain probe implanted in a patient, inaccordance with some embodiments of the present technology.

FIG. 5 is a table identifying representative indications, target neuralpopulations, rating scales, and improvement levels against which resultsobtained using techniques in accordance with the present technology maybe measured.

DETAILED DESCRIPTION

The present technology is directed generally to brain modulation viaelectrical signals, and associated systems and methods for addressingmotor dysfunctions and/or other patient indications. The electricalsignals generally have higher fundamental frequencies than do typicalsignals applied to the brain. For example, portions of the waveform havehigher fundamental frequencies, e.g., from 1.2 kHz to 500 kHz), andgenerally produce effective therapy with reduced or eliminatedundesirable side effects. Such side effects can include unwanted motorstimulation or blocking, dyskinesia, interference with sensoryfunctions, interference with speech, and/or interference with cognitivefunctions.

Specific details of embodiments of the technology are described belowwith reference to methods for modulating one or more neural populations(e.g., nerves or nerve populations) at target sites of a patient, andassociated implantable structures for providing the modulation. Althoughembodiments are described below with reference to modulating particularbrain structures, the modulation may in some instances be applied toother neurological structures and/or target populations of the brain,and/or other neurological tissues. Some embodiments can haveconfigurations, components, or procedures different than those describedin this section, and other embodiments may eliminate particularcomponents or procedures. A person of ordinary skill in the relevantart, therefore, will understand that the present disclosure may includesome embodiments with additional elements, and/or may include someembodiments without several of the features or elements shown anddescribed below with reference to FIGS. 1-4B.

In general terms, some embodiments of the present technology aredirected to producing a therapeutic effect that includes treatingpatient indications, for example, motor dysfunction, cognitivedysfunction, sensory dysfunction, speech dysfunction, neuropsychiatricdysfunction, and/or other dysfunction. Without being bound by theory,the therapeutic effect can be produced by quieting neural activity inthe brain, and/or other mechanisms. It is further expected that thetechniques described herein can produce more effective, more robust,less complicated, and/or otherwise more desirable results than canexisting brain stimulation techniques. It is also expected that thetechniques described below can produce therapeutic outcomes at least asgood as those associated with traditional techniques, with reduced oreliminated side effects.

Representative Systems

FIG. 1 schematically illustrates a representative treatment system 100for treating one or more neurologic diseases (and/or other conditions)arranged relative to the general anatomy of a patient's brain B. Thetreatment system 100 can include a signal delivery system 101 having asignal generator 102 (e.g., a pulse generator) and a signal deliverydevice 103 comprising one or more signal delivery element(s) 104 (e.g.,leads or probes that can include electrical signal delivery contacts).For purposes of illustration, a single signal delivery element 104 isshown in FIG. 1. The signal delivery element 104 can be positionedbilaterally (i.e., with one lead or probe in each hemisphere of thepatient), or unilaterally (i.e., with both leads or probes in the samehemisphere of the patient). When the signal delivery elements 104 arepositioned bilaterally, they can be implanted simultaneously or in astaged manner. The decision to deliver therapy bilaterally orunilaterally may be based on the disease or ailment being treated,and/or other factors (e.g., symptoms) of the patient. For example, insome embodiments, Parkinson's disease may be treated bilaterally (and/orunilaterally) and essential tremor disorders may be treated unilaterally(and/or bilaterally). As another example, dystonia can be treatedbilaterally and/or unilaterally. The signal generator 102 can beconnected or coupled to the signal delivery element(s) 104 via a signallink 105. The signal link 105 can include one or more components (e.g.,one or more leads, cables, extensions and/or wireless links) between thesignal delivery element(s) 104 and the signal generator 102. As shown inFIG. 1, the signal delivery element(s) 104 is configured to bepositioned in or at the patient's brain B to apply an electrical signalto the brain (e.g., to the white matter WM and/or gray matter GM). Thesignal generator 102 may be implanted subcutaneously within the patientP, e.g., at a subclavicular location, or at another suitable location,generally near the target neural population.

The signal delivery element(s) 104 can include a head 106 connected to aprobe 107, e.g., a deep brain probe. The head 106 can be positionedexternal to the patient's skull S, or within the patient's skull S, butexternal to the cortex C of the patient's brain B. The probe 107typically extends beneath the cortex C. The probe 107 can carry one ormore electrodes or contacts 108 that are electrically connected to thesignal generator 102 via corresponding conductors carried by the signallink 105 (or the signal link 105 can include a wireless link). A singleelectrode 108 can be activated to produce a monopolar signal (with aconductive outer housing of the signal generator 102 operating as areturn electrode), or multiple electrodes 108 (e.g., two, or more thantwo) can be activated to produce a bipolar or other multipolar signal.For example, in some embodiments, multiple electrodes 108 can beautomatically selected and used to deliver therapy to a particularregion between the selected electrodes. Furthermore, compared to using asingle electrode 108, using multiple electrodes 108 may, in someembodiments, help conserve energy by delivering more focused energy tothe particular region. Using multiple electrodes 108, compared to usinga single electrode 108, can also increase efficacy and/or decreaseundesirable side effects.

The signal generator 102 can transmit signals (e.g., electrical therapysignals) to the signal delivery element(s) 104 to produce a therapeuticeffect on the target nerves. As used herein, and unless otherwise noted,to “modulate,” “stimulate,” or provide “modulation” or “stimulation” tothe target nerves refers generally to producing a therapeutic effect viathe electrical therapy signal. Without being bound by theory, it isbelieved that in at least some embodiments, the electrical therapysignals can “quiet” target neurons, without inhibiting normal neuralactivity by the target neurons, and/or other neurons. It is furtherbelieved, without being bound by theory, that the frequency of thesignal, alone or in combination with other signal parameters, can beselected to produce the desired therapeutic effect. In at least someembodiments, other combinations of parameters may produce such effects.For example, selected pulse widths or ranges of pulse widths, canproduce such effects, over a variety of frequencies and/or amplitudes.

The signal generator 102 can include a machine-readable (e.g.,computer-readable) medium containing instructions for generating andtransmitting suitable therapy signals. The signal generator 102 and/orother elements of the treatment system 100 can include one or moreprocessors 109, memories 110 and/or input/output devices 111.Accordingly, the process of providing electrical signals, detectingphysiological parameters of the patient, adjusting the modulationsignal, and/or executing other associated functions can be performed bycomputer-executable instructions contained by, on, or incomputer-readable media located at the signal generator 102 and/or othersystem components. The signal generator 102 can include multipleportions, elements, and/or subsystems (e.g., for directing signals inaccordance with multiple signal delivery parameters) housed in a singlehousing, as shown in FIG. 1, or in multiple housings.

The signal delivery system 101 can include one or more sensing elements112 for detecting one or more physiological parameters of the patientbefore, during, and/or after the application of electrical therapysignals. In some embodiments, one or more of the sensing elements 112can be carried by the signal generator 102, the signal deliveryelement(s) 104, and/or other implanted components of the system 101. Insome embodiments, the sensing element(s) 112 can be an extracorporeal orimplantable device separate from the signal generator 102 and/or thesignal delivery element(s) 104. Representative sensing elements 112include one or more of: an accelerometer, a temperature sensor, animpedance sensor, a chemical sensor, a biosensor, an electrochemicalsensor, a hemodynamic sensor, an optical sensor and/or other suitablesensing devices. Some examples of physiological parameters that can bedetected by the sensing element(s) 112 include patient tremor, patientposition, patient posture, patient activity level, neurotransmitterconcentration, hormone concentration, local impedance, current, and/orvoltage levels, and/or any correlates and/or derivatives of theforegoing parameters (e.g., raw data values, including voltages and/orother directly measured values). The foregoing parameters can reflectpatient state and/or other patient-dependent variables, and/or variablesthat are patient-independent (e.g., time). Further details are includedin U.S. Pat. No. 8,355,797, which is incorporated herein by reference inits entirety.

The signal generator 102 can receive and respond to one or more inputsignals received from one or more sources. The input signals can director influence the manner in which the therapy and/or process instructionsare selected, executed, updated, and/or otherwise performed. The inputsignals can be received via one or more input/output devices 111 thatare carried by the signal generator 102 and/or distributed outside thesignal generator 102 (e.g., at other patient locations) while stillcommunicating with the signal generator 102. In some embodiments, theinput/output devices include wireless communication elements forcommunicating with external controllers or programmers, as described infurther detail later.

In some embodiments, the signal generator 102 can obtain power togenerate the therapy signals from an external power source 113. Theexternal power source 113 can transmit power to the implanted signalgenerator 102 using electromagnetic induction (e.g., RF signals). Forexample, the external power source 113 can include an external coil 114that communicates with a corresponding internal coil (not shown) withinthe implantable signal generator 102. The external power source 113 canbe portable for ease of use.

In some embodiments, the signal generator 102 can obtain the power togenerate therapy signals from an internal power source, in addition toor in lieu of the external power source 113. For example, theimplantable signal generator 102 can include a non-rechargeable batteryor a rechargeable battery to provide such power. When the internal powersource includes a rechargeable battery, the external power source 113can be used to recharge the battery. The external power source 113 canin turn be recharged from a suitable power source (e.g., conventionalwall power). When the internal power source includes a non-rechargeablebattery, the non-rechargeable battery can be removed from the patientand replaced after a set period of time or after receiving a low batteryindication. The non-rechargeable battery arrangement may not include asmany components as the rechargeable battery (e.g., may not include aninductive receiver), and thus the battery can be made larger to providea greater battery capacity (e.g., more battery cells) and thus a longeroperating lifespan.

As described above, the signal generator 102 may be implantedsubcutaneously within the patient P, e.g., at a subclavicular location,or at another suitable location, generally near the target neuralpopulation. The signal delivery element(s) 104 can be implanted at asimilar time (e.g., during the same procedure) and introduced into thepatient's head so as to be adjacent a selected brain region. Asdescribed in further detail below, the signal delivery element(s) 104can be intravascularly introduced or non-vascularly introduced into thepatient's head through, e.g., a burr hole drilled in the patient'scranium or by performing a craniotomy. Once the signal generator 102 andsignal delivery element(s) 104 are both implanted and connected orcoupled to one another, a functional testing procedure (e.g., to checkimpedance or the connection between the signal generator 102 and signaldelivery element(s) 104) may be performed.

Simply implanting the signal delivery element(s) 104 can, on its own(i.e., without any electrical stimulation), cause therapeutic effects insome patients, including, e.g., reduced undesirable movement (e.g.,tremors), reduced rigidity of movement, and/or a greater ability toinitiate movement. These therapeutic effects are temporary (e.g., canlast approximately 2-6 weeks) and are often referred to as the“insertion effect.” Accordingly, after the functional testing iscomplete, the practitioner may turn the signal generator 102 off untilafter the insertion effect has, or is expected to have, ceased.

Following the implantation procedure, the signal delivery parametersprovided by the signal generator 102 can be programmed or updated fromtheir default values. In some embodiments, programming the signalgenerator 102 is performed a period of time after the implantation(e.g., 6-8 weeks after implantation) to ensure any patient response tothe therapeutic signals delivered via the signal delivery element(s) 104are based on the therapeutic signal itself and not on other factors(e.g., the “insertion effect,” as described above. The signal generator102 can be programmed via a wireless physician's programmer orcontroller 118 (e.g., a physician's remote) and/or a wireless patientprogrammer or controller 119 (e.g., a patient remote). Generally, thepatient P has control over fewer parameters than does the practitioner.For example, the capability of the patient programmer 119 may be limitedto starting and/or stopping the signal generator 102, and/or adjustingthe signal amplitude. The patient programmer 119 may be configured toaccept therapy feedback information (e.g., tremor and/or other movementdata) as well as other variables, such as medication use.

In addition to or in lieu of portions of the foregoing implantationprocedure, the patient may undergo a trial period during which thefunctionality and/or the effectiveness of the therapeutic signalsdelivered via the signal delivery element(s) 104 are tested. Forexample, during the trial period, an external signal generator 115(e.g., a trial modulator) can be coupled to the signal deliveryelement(s) 104. For example, a practitioner (e.g., a physician and/or acompany representative) can use the external signal generator 115 tovary the modulation parameters provided to the signal deliveryelement(s) 104 in real time, and (a) determine if the patient respondsfavorably, and/or (b) select optimal or particularly efficaciousparameters. These parameters can include the location from which theelectrical signals are emitted, as well as the characteristics of theelectrical signals provided to the signal delivery element(s) 104. Insome embodiments, input collected via the external signal generator 115can be used by the clinician to help determine which parameters to vary.In a typical process, the practitioner uses a cable assembly 116 (or awireless link) to temporarily connect the external signal generator 115to the signal delivery element(s) 104. The practitioner can test theefficacy of the signal delivery element(s) 104 in an initial position.The practitioner can then disconnect the cable assembly 116 (e.g., at aconnector 117), reposition the signal delivery element(s) 104, andreapply the electrical signal. This process can be performed iterativelyuntil the practitioner obtains the desired signal parameters and/orposition for the signal delivery element(s) 104. Optionally, thepractitioner can move the partially implanted signal delivery element(s)104 without disconnecting the cable assembly 116. Furthermore, in someembodiments, the iterative process of repositioning the signal deliverydevice 103 and/or varying the therapy parameters may be eliminated.

When the signal delivery element(s) 104 is implanted, the patient P canreceive therapy via signals generated and transmitted by the externalsignal generator 115, generally for a limited period of time (e.g.,during the trial period). During this time, the patient wears the cableassembly 116 and the external signal generator 115 outside the body.Assuming the trial therapy is effective or shows the promise of beingeffective, the practitioner then replaces the external signal generator115 with the implanted signal generator 102. The implanted signalgenerator 102 may include default programs or therapy programs selectedbased on the experience gained during the trial period. Optionally, thepractitioner can also replace the signal delivery element(s) 104.

The implantable signal generator 102, the external signal generator 115and/or the connector 117 can each include one or more receiving elements120. Accordingly, the receiving elements 120 can be patient-implantableelements, or the receiving elements 120 can be integral with an externalpatient treatment element, device or component (e.g., the externalsignal generator 115 and/or the connector 117). The receiving elements120 can be configured to facilitate a simple coupling and decouplingprocedure between the signal delivery element(s) 104, the signal link105, the pulse generator 102, the external signal generator 115 and/orthe connector 117.

Representative Therapy Targets and Delivery Techniques

In some aspects of the present technology, one or more signal deliveryelement(s) 104 may be positioned within the patient's head, to modulateneurons at any suitable lobe or other structure of the cortex or deepbrain. Examples of deep brain regions that can be modulated include, forexample, the thalamus, the anterior thalamus, the ventrolateralthalamus, the internal segment of the globus pallidus (GPi), thesubstantia nigra pars reticulata (SNr), the subthalamic nucleus (STN),the external segment of the globus pallidus (GPe), the neostriatum, thecingulate cortex, the cingulate gyrus, and/or other regions. Otherexamples of deep brain regions that can be modulated include thehabenula (e.g., the lateral habenula (LHb)). In some embodiments,delivering electrical signals from signal delivery element(s) adjacentor in the habenula region, or more particularly the LHb region, cancause therapeutic effects via one or more of the mechanisms of action(e.g., quieting neural activity) identified above. In some embodiments,modulation may cause certain receptors (e.g., N-methyl-D-aspartate(NMDA) receptors) to be blocked, thereby allowing other neurons toactivate or fire at a relatively increased rate. In any of the foregoingembodiments, positioning the signal delivery element(s) adjacent to orin such deep brain regions and delivering an electrical therapy signalin accordance with the parameters described herein can cause therapeuticeffects via quieting neural activity and/or another mechanism of action.

In some embodiments, the signal delivery element(s) may be positioned inor adjacent to cortical structures/regions, in addition to, or in lieuof, placement at deep brain structures. The cortical structures can betargeted from an epidural location and/or a subdural location. Examplesof cortical structures/regions that can be modulated include thedorsolateral prefrontal cortex (e.g., to treat depression), the motorcortex (e.g., to treat movement disorders), the sensory cortex (e.g., totreat tinnitus), and/or other structures/regions, e.g., the motor strip,the sensory strip, and/or the pre-motor cortex. In some embodiments, thesignal delivery element(s) 104 can be delivered to any one of a numberof suitable vessels in order to place the electrodes adjacent the tissueto be stimulated, whether deep brain or cortical. Examples of veinsproviding access to deep brain structures include the inferior sagittalsinus, pericallosal sinus, cavernous sinus, sphenoid sinus, temporalbasal vein, and occipital veins. Examples of arteries providing accessto the deep brain include branches off the internal carotid or vertebralarteries. Examples of veins providing access to the cortex include thesuperior sagittal sinus, any of the superior cerebral veins branchingfrom the superior sagittal sinus (e.g., the lacuna, the frontopolarvein, the anterior frontal vein, the posterior frontal vein, theprecentral vein, the central vein, the anterior parietal vein, theposterior parietal vein, and the occipital vein), the superior sylvianvein, the vein of Labbe, the vein of Trolard, the inferior sagittalsinus, and any inferior cerebral veins branching off of the inferiorsagittal sinus, transverse sinus, and/or meningeal sinus. Examples ofarteries providing access to the cortex include any of the branches offthe external carotid arteries, the maxillary arteries, and/or themeningeal arteries. The vascular approach for introducing a signaldelivery device can allow the practitioner to reach more corticalstructures, especially in the folds of the cortex, than can be reachedvia cortical stimulation applied epidurally or subdurally. While theblood vessels are smaller in the deep brain structures, this approachcan also increase the possible target structures for deep brainstimulation, as described above.

In embodiments for which the signal delivery element(s) 104 areintroduced intravascularly, the jugular and/or femoral veins can be usedas intravascular access points from which the signal delivery element(s)104 can be delivered to the above-described veins, and the carotidand/or femoral arteries can be used as intravascular access points fromwhich the signal delivery element(s) 104 can be delivered to theabove-described arteries.

To access those brain regions that are not adjacent to easily-accessibleor navigable blood vessels, the treatment site may be accessed bynon-vascular techniques, e.g., via a burr hole drilled in the patient'scranium, or by performing a craniotomy. The technique can furtherinclude penetrating the parenchyma for deep brain stimulation (as shownin FIG. 1), or by epidurally or subdurally placing the signal deliveryelement(s) 104 along the cortex for cortical stimulation (as describedfurther below with reference to FIG. 2). Thus, it will be appreciatedthat intravascular and/or non-vascular placement techniques for thesignal delivery element(s) 104 can be utilized in procedures involvingmultiple brain regions. After the signal delivery element(s) 104 havebeen deployed, an electrical signal can be applied to directly affectthe neuronal cells at the target region.

FIG. 2 is a partially schematic, cross-sectional illustration of arepresentative signal delivery element(s) 104 placed at a cortical,rather than deep brain, location, in accordance with some embodiments ofthe present technology. In particular, the signal delivery element(s)104 can be positioned within the patient's dura D, in the subdural spaceDS, so as to lie along or adjacent to the gray matter GM of thepatient's cortex. In other embodiments, a signal delivery element(s) 104a can be placed within a sulcus S (e.g., the central sulcus Su) so as tobetter access neural populations within the folds of the patient'scortex. In still further embodiments, the signal delivery element(s) canbe positioned epidurally. Any of the foregoing cortical approaches aregenerally less invasive than a deep brain approach. Conversely, the deepbrain approach provides access (or closer access) to a greater selectionof neural populations than a cortical approach. The approach chosen fora particular patient can therefore depend upon one or more variables,including the patient's condition, and the type of neural structuresthat are expected to best respond to the treatment, among other factors.In at least some embodiments, whether the electrical signal is appliedto a cortical or deep brain location, an effect of the signal can be totarget areas of the brain that may suffer from a dopamine deficit. Thetarget area can be at a site of dopamine production, and/or at a site ina neural circuit that includes dopamine-producing areas.

Representative Signal Parameters

The electrical stimulation pulses delivered via the signal deliveryelement(s) 104 to a brain region of the patient can include a variety ofwaveforms. In some embodiments, the waveform can include a monophasicwaveform, a charge balanced biphasic waveform, a charge imbalancedbiphasic waveform and/or a charge balanced biphasic waveform with adelay (e.g., an interphasic delay between the cathodic phase and theanodic phase of the pulse). In some embodiments, it is believed thatcharge balanced biphasic waveforms at frequencies from 1.2 kHz to 500kHz and with an interphasic delay can provide more efficaciousneuromodulation, while also mitigating the risk of damaging adjacenttissue, when used to treat the brain region. It is believed that chargebalanced biphasic waveforms with an interphasic delay can also allow fora distinct mechanism of action (e.g., quieting overly active neuronalcells) for treating the brain region of the patient, compared to otherconventional brain stimulation techniques.

In any of the foregoing embodiments, aspects of the therapy provided tothe patient may be varied within suitable ranges to produce beneficialresults for patients suffering from motor and/or other disorders. Forexample, the location of the signal delivery (and in particular, thelocations of active contacts or electrodes) can be varied by moving thesignal delivery device and/or by selecting different electrodes orcontacts carried by the signal delivery device. Other characteristics ofthe applied signal can also be varied. For example, the signal can bedelivered at a frequency of from about 1.2 kHz to about 500 kHz, and inparticular embodiments, from about 1.5 kHz to about 500 kHz, from about1.2 kHz to about 250 kHz, from about 1.2 kHz to about 100 kHz, fromabout 1.2 kHz to about 50 kHz, or from about 1.2 kHz to about 25 kHz. Infurther particular embodiments, the signal can be provided atfrequencies greater than 4 kHz or greater than 5 kHz, e.g., from about 5kHz to about 20 kHz, or from about 5 kHz to about 15 kHz, or from about5 kHz to about 10 kHz. In further embodiments, the frequency range canbe or extend from 5 kHz, 6 kHz, 7 kHz, 8 kHz, 9 kHz or 10 kHz to any of15 kHz, 30 kHz, 50 kHz, or 100 kHz. In further embodiments, and asdescribed in more detail below, frequencies from about 1.2 kHz to about500 kHz can be used in tandem with lower frequencies (below 1.2 kHz),such as frequencies less than about 1000 kHz, or less than about 250 Hz,or from about 10 Hz to about 150 Hz, or from about 60 Hz to about 130Hz.

For the frequencies or frequency ranges disclosed above between 1.2 kHzand 500 kHz, the amplitude of the signal can range from about 0.1 mA toabout 20 mA in some embodiments, and in some embodiments, can range fromabout 0.1 mA to about 15 mA, or about 0.1 mA to about 10 mA, or about0.1 mA to about 7.5 mA, or about 0.1 mA to about 4 mA or about 0.5 mA toabout 10 mA, or about 0.5 mA to about 4 mA, or about 4 mA to about 7 mA,or about 4 mA to about 10 mA, or about 2 mA to about 5 mA, or about 3.0mA to about 5.0 mA, or about 2 mA to about 4 mA, or about 4 mA to about6 mA, or about 0.5 mA to about 2.5 mA. In some embodiments, theamplitude of the signal may be selected based on a variety of factorsincluding the mechanism of action, the target stimulation site (e.g.,the STN or GPi), expected efficacy of the treatment, expected sideeffects, expected time for an electrical signal to take effect. Inanother example, a higher amplitude may be used during later phases ofthe treatment, e.g., if the patient's response to a lower amplitudesignal begins to fade over time. As yet another example, the higheramplitude may be used when the signal is applied to a particularstructure (e.g., the STN) known or expected to respond more favorably(e.g., to produce no or less undesirable side effects) to the higheramplitude. The lower amplitude may be used when the signal is applied toa particular structure (e.g., the GPi) known or expected to respond morefavorably to the lower amplitude. In still another embodiment, a higheramplitude (e.g., an amplitude of about 5-7 mA) may be used when thesignal is intended to cause a therapeutic effect by exciting/activatingneural elements. In a related example, a lower amplitude (e.g., anamplitude of about 2-5 mA) may be used when the signal is intended tocause a therapeutic effect by inhibiting/suppressing neural elements.

An advantage of some embodiments of the present technology is that usingthe above-noted frequency ranges of about 1.2 kHz to about 500 kHzallows a physician, clinician, and/or other personnel to use a broaderrange of amplitudes, compared to when a lower frequency range of lessthan about 1200 Hz or 1000 Hz is used. This can be particularlybeneficial because the amplitudes needed to treat a particular patientmay change, continuously or otherwise over the course of time. Forinstance, in some patients the amplitude needs can increase over time,as indicated above. Accordingly, the expected increase in availableamplitude range associated with treating the patient at the 1.2 kHz to500 kHz frequency range can allow the patient to receive treatment overa longer period of time and/or with increased efficacy and/or decreasedside effects.

The pulse width of the signal can vary over a suitable range from about1 microsecond to about 400 microseconds. The particular maximum pulsewidth value selected is established by the frequency of the signal, byinter-phase intervals, and by the phase nature of the signal (monophasicor biphasic). Within the range capped by the maximum value, the pulsewidth can be selected based on neural response, reduction in sideeffects and/or other factors, such as energy consumption. Other signalparameters (e.g., frequency, duty cycle, amplitude, waveform, etc.) mayalso be selected based on the same variety of factors.

As used herein, the pulse width of the signal refers to just thecathodic phase of the pulses, or alternatively just the anodic phase. Infurther particular examples, the pulse width can vary from about 1microsecond to about 333 microseconds. For example, in some embodiments,the pulse width can be about 2 microseconds, about 3 microseconds, orabout 4 microseconds. In some embodiments, the pulse width can rangefrom about 10 microseconds to about 333 microseconds, or from about 25microseconds to about 166 microseconds, or from about 33 microseconds toabout 100 microseconds, or from about 50 microseconds to about 166microseconds, or from about 30 microseconds to about 35 microseconds.The pulses can be delivered in a biphasic manner (e.g., for chargebalancing), with the anodic and anodic pulses symmetric or asymmetric.The specific values selected for the foregoing parameters may vary frompatient to patient and/or from indication to indication and/or on thebasis of the selected target neural population, and/or on the basis ofthe electrode location. In addition, the methodology may make use ofother parameters, in addition to or in lieu of those described above, tomonitor and/or control patient therapy. For example, in cases for whichthe pulse generator includes a constant voltage arrangement rather thana constant current arrangement, the current values described above maybe replaced with corresponding voltage values.

For any of the frequencies, frequency ranges, amplitude ranges, pulsewidth ranges, or combinations thereof, disclosed above, in someembodiments, the duty cycle may be varied e.g., to be less than 100%, orless than 75% or less than 50%. The lengths of the on/off periods for agiven duty cycle can also be varied. For example, patients may haveimproved therapeutic effects (e.g., improved motor functioning) anddecreased unwanted side effects (e.g., motor side effects, sensory sideeffects, and/or general side effects), any of which can persist forsignificant periods after the stimulation has been halted. Accordingly,the signal generator can be programmed to halt stimulation for periodsof up to several seconds, minutes or hours, with appropriate allowancesfor the time necessary to re-start the beneficial effects. Thisarrangement can significantly reduce system power consumption, comparedto systems with higher duty cycles, and compared to systems that haveshorter off periods.

In addition to or in lieu of duty cycling, the therapy being deliveredto a patient can vary between a first signal (e.g., at 1.2 kHz to 500kHz) and a second signal having a lower frequency (e.g., less than 1200Hz, or less than 1000 Hz, and in some embodiments, less than 130 Hz).The two signals can each be on for equal time durations or differenttime durations. For example, the first signal can be on for 10 secondsand can be followed by the second signal being on for 10 seconds, or thefirst signal can be on for 30 seconds and can be followed by the secondsignal being on for 10 seconds (or vice versa). The first signal and thesecond signal can be iteratively interleaved with one another throughoutat least a portion of a therapy session.

It has been observed that patients can exhibit improved therapeuticeffects (e.g., improved motor functioning) and decreased unwanted sideeffects (e.g., motor side effects, sensory side effects, and/or generalside effects) that persist for periods of time after the first (e.g.,higher frequency) therapy signal has halted and while the second (e.g.,lower frequency) therapy signal is active. In some examples, theimproved therapeutic effects can persist for 5-30 minutes, and up toseveral hours or even days. Accordingly, the signal generator can beprogrammed to transition between the first signal and the second signalfor periods of up to several seconds, minutes or hours, with appropriateallowances for the time necessary to re-start the improved therapeuticeffects (e.g., via the first signal). This arrangement can significantlyreduce system power consumption, compared to systems with higher dutycycles and/or shorter off periods.

In view of the foregoing, the duty cycle of the overall signal may bevaried, e.g., to be less than 100%, or less than 75%, or less than 50%,such that the signal being delivered to a patient can vary between thefirst signal, the second signal, and an off period. The first signal,second signal, and off period can each be in effect for equal timedurations or different time durations, as described above. In someembodiments, the second signal can extend the improved benefits for alonger time period, compared to the time period during which benefitsare extended when the signal is halted. Accordingly, the combination ofthe first signal, the second signal, and the off period can reduce(e.g., optimally reduce) power consumption, compared to systems withhigher duty cycles and/or shorter off periods.

In any of the foregoing embodiments, the parameters in accordance withwhich the signal generator 102 provides signals can be adjusted duringportions of the therapy regimen. For example, the frequency, amplitude,pulse width, and/or signal delivery location can be adjusted inaccordance with a pre-set therapy program, patient and/or physicianinputs, and/or in a random or pseudorandom manner.

Representative Methods

FIG. 3 illustrates a process 300 for treating patients in accordancewith some embodiments of the present technology. Some or all elements ofthe process can be conducted via machine-readable instructions that arecontained on or in any suitable element or elements of the system (e.g.,the implanted signal generator 102, the external signal generator 115,the physicians programmer or controller 118, and/or the patientsprogrammer or controller 119, described above with reference to FIG. 1).Block 302 includes identifying a patient indication amenable totreatment via the techniques disclosed herein. Representativeindications include tremor (e.g., essential tremor, stroke-inducedtremor, and/or other tremors), and Parkinson's disease (which caninclude bradykinesia, akinesia, dyskinesia, tremor, rigidity, posturalabnormalities, and/or gait abnormalities). In some embodiments, theindication can include other motor disorders, non-motor disorders,and/or other neurological conditions, depending upon the patient. Forexample, representative non-movement disorders can include sensorydisorders, such as chronic pain. Other representative disorders includespeech disorders, epilepsy, and neuropsychiatric disorders.

In block 304, the process includes selecting a target neural population.The selected neural population will depend at least in part upon thepatient indication to be treated. In some embodiments, the targetlocation can include the thalamus for example, and can include othersuitable locations in other embodiments. In some cases, the patient'scondition may be treated by modulating any of several different neuralpopulations including those listed herein, with the target populationselected based on factors that include its integrity or level of neuraldamage to the population, how accessible the neural population is,and/or the likelihood that the neural population will respond favorablyto the therapy signal.

At block 306, the process includes selecting a signal delivery device.For example, the process can include selecting the signal deliverydevice to include a deep-brain probe, a cylindrical cortical lead, acortical paddle lead, and/or another suitable device. The deviceselected for a particular patient will depend on a number of factors,including which target neural population is selected at block 304, thepatient's condition (e.g., the patient's tolerance for invasiveprocedures), and/or other factors.

At block 308, the signal delivery device is implanted so that thecontacts, electrodes, and/or other elements that deliver the electricaltherapy signal to the target neural population, are properly positioned.In some embodiments, during an initial phase (e.g., the trial period) ofthe process following the signal delivery device implant, the patientcan receive therapeutic signals via an external signal generator, asdescribed above with reference to FIG. 1. During this phase, the patientcan be assessed for responsive behavior (block 310). If the patient is a“non-responder” the process can include selecting a new therapy for thepatient (block 312). If the patient is a “responder”, the process caninclude implanting a signal generator (block 314) and connecting theimplanted signal generator to the signal delivery device implanted atblock 308, or to a newly implanted signal delivery device. Or, as wasalso discussed above with reference to FIG. 1, the practitioner canimplant a signal generator without first using an external pulsegenerator. Whether or not the patient undergoes a trial period with anexternal signal generator, the implanted signal generator can beimplanted at a subclavicular location as discussed above with referenceto FIG. 1, or at other suitable locations. Such locations can include acranial location (e.g., with the implanted signal generator implantedbeneath the scalp, but external to the skull, or within the skull), or acochlear location. In any of these examples, the signal generator can beshaped and sized to allow implantation at the desired location. Asbattery and electronic circuitry technologies continue to evolve, it isexpected that the signal generators can be made smaller, thus increasingthe selection of sites suitable for implantation.

At block 316, the process can include determining whether the modulationparameters with which the therapy signal is delivered are optimized, orat least improved, compared to a suitable baseline (e.g., the patient'sinitial condition). If not, then at block 318 the parameters areadjusted and the patient's response reassessed. If the parameters areoptimized, then the process can include continuing to apply the therapyvia the implanted pulse generator (block 320).

In some embodiments, the process can return to block 316 to determinewhether the parameters are, or remain, optimized. This loop can be basedon the passage of time, and/or other factors. For example, theparameters can be assessed at regular intervals, measured on a scale ofseconds, minutes, hours, days or weeks. In addition to or in lieu of atime-based feedback process, the process can respond to informationcorresponding more directly to the efficacy of the patient's therapy.For example, if the patient has been suffering from a tremor, and anaccelerometer indicates that the initially suppressed tremor hasreappeared, then the process can return to blocks 316 and 318 to adjustthe parameters for improved therapeutic efficacy. In some embodiments,the feedback loop can respond to inputs other than accelerometer inputs,e.g., as described above with reference to FIG. 1. In some embodiments,other feedback mechanisms can include receiving electrophysiologicalsignals from the brain, for example the subthalamic nucleus (STN) and,based upon the feedback, change signal delivery parameters such as anamplitude, frequency and/or pulse width.

FIGS. 4A and 4B illustrate a representative lead or probe 107 implantedin a representative patient's brain B in accordance with someembodiments of the present technology. FIG. 4A is an image taken in theplane of the probe 107, indicating that a tip 121 of the probe 107 islocated at the subthalamic nucleus (STN) of the patient's brain. FIG. 4Bis an end-on view of the probe 107 shown in FIG. 4A.

After the patient was implanted with the probe 107 at the location shownin FIGS. 4A and 4B, a therapy signal was directed to the probe 107 at afrequency of about 10 kHz, a pulse width of 30 microseconds, and anaverage amplitude of about 4 mA. The patient, who was suffering fromuncontrolled hand tremors, responded nearly immediately to themodulation signal, with the tremors ceasing. When the therapy signal wasdiscontinued (during the course of a short, intraoperative procedure),the tremor returned. The intraoperative process (which includedaccounting for insertion effects, described above) was sufficient todetermine that the patient qualified as a responder, and so the patientreceived an implant, in accordance with the process described above withreference to FIG. 3.

During a typical intraoperative procedure, the patient can be evaluatedon the basis of one or more suitable parameters, including for example,head tremor, face tremor, voice tremor, and/or upper extremity tremor,rigidity, akinesia, dyskinesia, speech impairment, etc. The upperextremity tremor can be evaluated as the patient performs multipletasks. Representative tasks include moving the right upper extremityforward, moving the right upper extremity to a wing position, moving theleft upper extremity to a wing position, moving the right upperextremity kinetically, and/or moving the left upper extremitykinetically. The patient's lower extremity tremor, Archimedes spiraltremor, hand writing, performance on a dot approximation task, and/orother tasks can also be evaluated during the intraoperative process.

As described above, an expected advantage of embodiments of the presenttechnology (based at least in part on a clinical comparison of patientswho received intraoperative conventional therapy at a frequency of 130Hz, and patients who received intraoperative therapy at a frequency of10 kHz) is that the side effects experienced by the patient will bereduced compared to those associated with conventional brain stimulationtechniques. Such side effects can manifest as motor side effects,sensory side effects, and/or general side effects. Typical motor sideeffects that are expected to be reduced or eliminated include twitchingeffects and dysarthria. Typical sensory side effects that are expectedto be reduced or eliminated including dysesthesia and/or paresthesia,hypoesthesia, adverse effects on temperature sensation, and/or pain. Forexample, many patients receiving traditional deep brain stimulationperceive paresthesia in the face, arms, or other areas of the body. Itis expected that therapy in accordance with the parameters describedherein can produce effective results, without such side effects.

The presently disclosed therapy can also reduce or eliminate moregeneral side effects while maintaining or improving typical therapy.Typical general side effects expected to be reduced or eliminatedinclude blurring sensations, light-headedness, dizziness, vision changesand/or mood changes and alterations. Further representative side effectsthat may be reduced or eliminated include deficient neurotransmitterconcentrations (e.g., for dopamine and/or other neurotransmitters).Additional side effects that may be avoided or reduced via treatment inaccordance with embodiments of the present technology include adverselyaffecting the patient's speech, gait, expressions, balance, memory,emotions and/or cognitive abilities, in addition to or in lieu of themotor effects described above. Representative cognitive processes thatare not expected to be affected by the foregoing therapy techniquesinclude forming thoughts, and/or selecting thoughts from multiplepossible thoughts in an organized rather than confused manner. Inaddition, the present therapy is not expected to contribute negativelyto anxiety, depression, addictions, and/or emotional disorders in thepatient. In fact, in some embodiments it is expected that emotionaldisorders, anxiety, depression, addiction, and the emotions resultingfrom these conditions can be reduced, for example when the targetlocation is at or near the habenula. These effects can be particularlysignificant because more traditional or conventional brain stimulation(e.g., at frequencies less than 1200 Hz) can result in many of theabove-identified side effects. These lower frequencies, when usedwithout interleaving higher frequency signals, can worsen a patient'sspeech and over time cause further speech-related issues. Accordingly,one of the benefits of embodiments of the present technology usinghigher frequencies (e.g., 1.2 kHz to about 500 kHz) is that thetechnology can improve or at least not worsen the patient's pre-existingspeech deficit.

The foregoing example describes an instance in which the therapy is usedto treat a disorder or dysfunction without causing or worsening a sideeffect (e.g., a speech deficit). In still further embodiments, what isconsidered a side effect of treating a disorder may itself be a disorderand/or a symptom of a disorder. For example, a patient may have adisorder that is or includes a speech deficit. Embodiments of thepresent technology can be used to directly treat the speech deficit, byapplying a therapy signal having parameters as described herein. This isin direct contrast to the typical patient experience with devicesadministering therapy signals at a frequency of less than 1.2 kHz. Suchexperiences can include deliberately turning the device off beforespeaking in order to avoid the speech impediments created by the therapysignal. Instead, embodiments of the present technology can use afrequency signal of 1.2 kHz or above to improve, rather than exacerbate,the patient's speech deficit.

Still further, in at least some conventional treatment modalities (e.g.,using an electrical therapy signal with a frequency of less than 1.2kHz), improving one symptom and/or side effect results in create orworsening another symptom and/or side effect. By contrast, it isbelieved that therapies applied accordance with embodiments of thepresent technology can result in improving at least one symptom and/orside effect without creating or worsening another symptom and/or sideeffect.

As discussed above, an expected advantage of embodiments of the presenttechnology, when compared to traditional or conventional brainstimulation techniques (e.g., at frequencies less than 1200 Hz or lessthan 1000 Hz), is that the present technology can allow a physician oroperator to use a broader range of amplitudes for stimulation. This samebenefit holds true for side effects, as the amplitude window withinwhich detrimental side effects are inhibited, or at least notexaggerated, is greater when higher frequency stimulation (as disclosedherein), is used, compared to when lower frequency stimulation ofconventional technologies is used.

As discussed above, another expected advantage of embodiments of thepresent technology, when compared to traditional or conventional brainstimulation techniques, is that the present technology can producegreater efficacy. For example, treatment in accordance with embodimentsof the present technology provided an increased effectiveness to improvea patient's speech and/or rigidity symptoms, compared to conventionalbrain stimulation techniques. Without being bound by theory, theincreased efficacy may be attributed to a possible mechanism of actionby which embodiments of the present therapy operate, which is to quietoverly active neuronal cells.

In addition to producing greater efficacy, therapy signals in accordancewith the present technology may allow the practitioner to treat motorand/or other dysfunctions by targeting brain structures that are nottypically targeted using conventional therapies. For example,traditional deep brain stimulation typically is not directed to thehippocampus, so as to avoid unintended detrimental effects on thepatient's memory. The present therapy may avoid such detrimental effectsand therefore may provide one or more additional options for patienttreatment.

More generally, embodiments of the present technology are directed toproviding an effective therapy to a patient via an electrical therapysignal, without the signal generating non-therapeutic (e.g.,undesirable) side effects, or generating such side effects, but at areduced level compared with the side effects associated with electricalstimulation at frequencies below 1.2 kHz. What constitutes an “effectivetherapy” typically varies from indication to indication, but in manyinstances, has a value that is commonly accepted by practitioners in thefield. For example, for Parkinson's disease, the Unified Parkinson'sDisease Rating Scale is used to measure the patient's condition, and adecrease of at least 30% on Part 3 of the scale is considered aneffective therapy. For psychiatric disorders, the Hamilton DepressionRating is used, and a reduction of 50% is generally considered to beeffective therapy. The foregoing are two representative examples, andFIG. 5 provides further representative examples, along with targetlocations at which the therapy may be delivered, and representative sideeffects that are reduced or eliminated via therapy in accordance withthe present technology. The side effects do not include an “onsetresponse,” which is a brief sensory response typically experienced bypatients at the beginning of a therapy treatment. While the examplesprovided herein indicate representative efficacy measures, andrepresentative side effects, the technology need not be specificallylimited thereby, unless noted.

Certain aspects of the present technology described in the variousembodiments above may be simplified, modified, combined or eliminated inother embodiments. For example, features described under any of theheadings above may be combined with features described under otherheadings. Therapies directed to addressing particular indications may becombined. The thalamus, or structures within the thalamus, may betargeted for addressing motor dysfunctions, as described above. In someembodiments, the thalamus may be targeted for addressing sensorydefects, including chronic pain. Because the thalamus includes centersfor sensing pain, touch, hot, cold, and texture, applying deep brainstimulation to the thalamus may address defects associated with any ofthe foregoing senses, including chronic pain indications. Further, whileadvantages associated with certain embodiments have been described inthe context of those embodiments, other embodiments may also exhibitsuch advantages, and not all embodiments need necessarily exhibit suchadvantages to fall within the scope of the present disclosure.

To the extent any materials incorporated herein by reference conflictwith the present disclosure, the present disclosure controls. As usedherein, the term “and/or”, as in “A and/or B” covers A alone, B alone,and both A and B. As used herein, the term “about” refers to a valuewithin a range of ±10% of the identified value, unless otherwise noted.

The following examples provide further representative embodiments of thepresently disclosed technology.

1. A method for treating a patient, comprising: applying a therapysignal to a patient, via at least one electrode at a subdural orepidural location at the patient's brain, to provide effective therapythat reduces or eliminates effects of a patient disorder, without thetherapy signal inducing any non-therapeutic side effects, wherein thetherapy signal has a frequency in a frequency range from 1.2 kHz to 500kHz, an amplitude in an amplitude range from 0.1 to 20 mA, and a pulsewidth in a pulse width range from 1 microsecond to 400 microseconds.

2. A method for treating a patient, comprising: programming a signalgenerator to apply a therapy signal to a patient, via at least oneelectrode at a subdural or epidural location of the patient's brain, toprovide effective therapy that reduces or eliminates effects of apatient disorder, without the therapy signal inducing anynon-therapeutic side effects, wherein the therapy signal has a frequencyin a frequency range from 1.2 kHz to 500 kHz, an amplitude in anamplitude range from 0.1 to 20 mA, and a pulse width in a pulse widthrange from 1 microsecond to 400 microseconds.

3. A system for treating a patient, comprising: an signal deliverydevice configured to be implanted at a subdural or epidural location ofthe patient's brain, and an implantable pulse generator, coupleable tothe signal delivery device and programmed with instructions that, whenexecuted direct a therapy signal to a patient, via the signal deliverydevice, to provide effective therapy that reduces or eliminates effectsof a patient disorder, without the therapy signal inducing anynon-therapeutic side effects, wherein the therapy signal has a frequencyin a frequency range from 1.2 kHz to 500 kHz, an amplitude in anamplitude range from 0.1 to 20 mA, and a pulse width in a pulse widthrange from 1 microsecond to 400 microseconds.

We claim:
 1. A method for treating a patient, comprising: applying anelectrical signal generated by an implanted signal generator to apatient, via at least one electrode at the patient's subthalamic nucleus(STN), to reduce or eliminate effects of a patient disorder, without theelectrical signal inducing paresthesia and without the electrical signalimpeding speech, wherein the electrical signal has a frequency of 10kHz, an amplitude in an amplitude range from 0.1 to 7.5 mA, and a pulsewidth in a pulse width range from 30 microsecond to 35 microseconds. 2.The method of claim 1 wherein the patient disorder includes at least oneof: a motor disorder, a sensory disorder or a neuropsychiatric disorder.3. The method of claim 1 wherein the therapy signal does not induce anysensory side effects, cognitive side effects or motor side effects. 4.The method of claim 3 wherein the motor side effects include at leastone of twitching or dysarthria.
 5. The method of claim 3 wherein thesensory side effects include at least one of dysesthesia, hypoesthesia,adverse effects on temperature sensation, or pain.
 6. The method ofclaim 3 wherein the cognitive side effects include adversely affectingat least one of forming thoughts, selecting thoughts from multiplepossible thoughts in an organized manner, or initiating motor actions.7. The method of claim 1 wherein the patient disorder includesParkinson's disease.
 8. The method of claim 1 wherein the therapy signaldoes not induce blurring sensations, light-headedness, dizziness, visionchanges, mood changes or mood alterations.
 9. A method for treating apatient, comprising: applying an electrical signal generated by animplanted signal generator to a patient, via at least one electrode atthe patient's subthalamic nucleus (STN), to reduce or eliminate effectsof a patient disorder, without the electrical signal impeding speech,wherein the electrical signal has a frequency of 10 kHz, an amplitude inan amplitude range from 0.1 to 20 mA, and a pulse width in a pulse widthrange from 1 microsecond to 400 microseconds.
 10. The method of claim 9wherein the patient disorder includes at least one of: a motor disorder,a sensory disorder or a neuropsychiatric disorder.
 11. The method ofclaim 9 wherein the therapy signal does not induce any sensory sideeffects, cognitive side effects or motor side effects.
 12. The method ofclaim 11 wherein the motor side effects include at least one oftwitching or dysarthria.
 13. The method of claim 11 wherein the sensoryside effects include at least one of dysesthesia, paresthesia,hypoesthesia, adverse effects on temperature sensation, or pain.
 14. Themethod of claim 11 wherein the cognitive side effects include adverselyaffecting at least one of forming thoughts, selecting thoughts frommultiple possible thoughts in an organized manner, or initiating motoractions.
 15. The method of claim 9 wherein the patient disorder includesParkinson's disease.
 16. The method of claim 9 wherein the therapysignal does not induce blurring sensations, light-headedness, dizziness,vision changes, mood changes or mood alterations.
 17. The method ofclaim 9 wherein the amplitude is from 0.1 mA to 10 mA.
 18. The method ofclaim 9 wherein the amplitude is from 0.1 to 4 mA.
 19. A method fortreating a patient, comprising: applying an electrical signal generatedby an implanted signal generator to a patient, via at least oneelectrode at the patient's subthalamic nucleus (STN), to reduce oreliminate effects of a patient disorder, without the electrical signalinducing paresthesia, wherein the electrical signal has a frequency in afrequency range from 5 kHz to 20 kHz, an amplitude in an amplitude rangefrom 0.1 to 20 mA, and a pulse width in a pulse width range from 1microsecond to 400 microseconds.
 20. The method of claim 19 wherein thepatient disorder includes at least one of: a motor disorder, a sensorydisorder or a neuropsychiatric disorder.
 21. The method of claim 19wherein the therapy signal does not induce twitching or dysarthria. 22.The method of claim 19 wherein the therapy signal does not induce sideeffects including adversely affecting at least one of forming thoughts,selecting thoughts from multiple possible thoughts in an organizedmanner, or initiating motor actions.
 23. The method of claim 19 whereinthe frequency is 5 kHz.
 24. The method of claim 19 wherein the frequencyis 10 kHz.
 25. The method of claim 19 wherein the frequency is in arange from 5 kHz to 15 kHz.
 26. The method of claim 19 wherein theamplitude is from 0.1 mA to 7 mA.
 27. The method of claim 19 wherein theamplitude is from 0.1 to 4 mA.
 28. The method of claim 19, furthercomprising adjusting at least one of the frequency, pulse width oramplitude of the electrical signal in response to feedback received froma sensor.
 29. A method for treating a patient, comprising: applying anelectrical signal generated by an implanted signal generator to apatient, via at least one electrode at the patient's subthalamic nucleus(STN), to reduce or eliminate effects of a patient disorder, without theelectrical signal inducing paresthesia, wherein the electrical signalhas a frequency of 10 kHz, an amplitude in an amplitude range from 0.1to 7.5 mA, and a pulse width in a pulse width range from 30 microsecondto 35 microseconds.